Heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism

Han, Jia Xi; Ng, Garrett Z.; Cecchini, Paola; Chionh, Yok Teng; Saeed, Muhammad; Næss, Lisbeth Meyer; Joachim, Michael V.; Blandford, Lucy E.; Strugnell, Richard A.; Colaço, Camilo; Sutton, Philip

doi:10.1016/j.vaccine.2016.02.001

Cited by 4 publications

(9 citation statements)

References 39 publications

(31 reference statements)

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“…6 As TLR2 and TLR4 are both dependent on MyD88 this is consistent with the original premise that HspC induce immunity via activation of cell surface TLR. However there remain several unanswered questions.…”

Section: Hspc Vaccine Induced Cellular Responsesupporting

confidence: 86%

“…In a study recently published in Vaccine we reported the first evaluation of the mechanism of action of an HspC vaccine. 6 This showed that, as predicted, the cellular response of mice to neisserial HspC vaccines was completely dependent on the TLR adaptor protein MyD88.…”

Section: Introductionmentioning

confidence: 60%

“…9 We have not yet determined why a Th17 response was not detectable following neisserial HspC vaccination or direct stimulation of mouse splenocytes. 6 However it is perhaps worth noting that we have previously detected an increased Th17 response at the site of infection in mice prophylactically vaccinated with HspC against Helicobacter pylori, 5 which suggests the ability of HspC to induce a Th17 response might either vary between the bacterial source of the formulation, or require a live in vivo challenge (something we have not performed for the Neisseria studies).…”

Section: Hspc Vaccine Induced Cellular Responsementioning

confidence: 93%

“…6 If anything, the response to these vaccines was greater in mice lacking the ability to signal via all the MyD88-dependent TLR than in wildtype mice. This was surprising, given our initial premise that HspC vaccines adjuvant an immune response via TLR activation.…”

Section: Antibody Responsementioning

confidence: 99%

“…6 We thus evaluated IL-12 secretion (as a key driver of Th1-immunity) in the RAW264.7 cells we generated for this current study. Unfortunately we found that RAW264.7 cells do not secrete IL-12 when activated via TLR4, as previously reported.…”

Section: Hspc Vaccine Induced Cellular Responsementioning

confidence: 99%

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Activation of TRIF-dependent and independent immune responses by neisserial heat shock protein complex vaccines

Han

Colaço³

et al. 2016

Human Vaccines & Immunotherapeutics

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ASBTRACT Heat shock protein Complex (HspC) vaccines are composed of Hsp purified from pathogenic bacteria along with their chaperoned protein cargo. Mouse studies have shown that HspC vaccines can induce a strong immune response against pathogenic bacteria without addition of an exogenous adjuvant. These vaccines are now entering clinical trials. It was predicted, but not previously tested, that HspC vaccines induce an immune response due to the activation of Toll-Like Receptors (TLR) by their component Hsp. Recently we tested this supposition and found that while this held true for the cellular response to neisserial HspC vaccines, strong antigen-specific antibody responses were surprisingly generated in mice deficient in MyD88 and thus most TLR signaling. This suggested an unidentified mechanism by which HspC vaccines induce an antibody response. We have now examined the antigenic profile of this response and found no evidence that this is due to the induction of T-independent antibodies. Examination of the MyD88-dependent signaling pathways involved in the cellular response to neisserial HspC showed that both TRIF-dependent and TRIF-independent pathways are activated, each resulting in the secretion of different cytokines. Hence the mechanism of action of HspC vaccines is clearly more complicated than originally thought.

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Section: Hspc Vaccine Induced Cellular Responsesupporting

confidence: 86%

Section: Introductionmentioning

confidence: 60%

Section: Hspc Vaccine Induced Cellular Responsementioning

confidence: 93%

Section: Antibody Responsementioning

confidence: 99%

Section: Hspc Vaccine Induced Cellular Responsementioning

confidence: 99%

See 3 more Smart Citations

Activation of TRIF-dependent and independent immune responses by neisserial heat shock protein complex vaccines

Han

Colaço³

et al. 2016

Human Vaccines & Immunotherapeutics

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Toll-Like Receptor 4 Interactions with Neisseria

Christodoulides

2020

The Role of Toll-Like Receptor 4 in Infectious and Non Infectious Inflammation

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Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands

Moyle

2017

Bioconjugate Chem.

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Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g., proteins and polysaccharides). These antigens, however, often elicit poor immunological responses, necessitating the use of adjuvants. Immunostimulatory adjuvants have the capacity to activate antigen presenting cells directly through specific receptors (e.g., Toll-like receptors (TLRs)), resulting in enhanced presentation of antigens as well as the secretion of proinflammatory chemokines and cytokines. Consequently, innate immune responses are amplified and adaptive immunity is generated. Recently, site-specific conjugation of such immunostimulatory adjuvants (e.g., TLR ligands) onto defined antigens has shown superior efficacy over unconjugated mixtures, suggesting that the development of chemically characterized immunostimulatory adjuvants and optimized approaches for their conjugation with antigens may provide a better opportunity for the development of potent, novel vaccines. This review briefly summarizes various TLR agonists utilized as immunostimulatory adjuvants and focuses on the development of techniques (e.g., recombinant, synthetic, and semisynthetic) for generating adjuvant-antigen fusion vaccines incorporating peptide or protein antigens.

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Heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism

Cited by 4 publications

References 39 publications

Activation of TRIF-dependent and independent immune responses by neisserial heat shock protein complex vaccines

Activation of TRIF-dependent and independent immune responses by neisserial heat shock protein complex vaccines

Toll-Like Receptor 4 Interactions with Neisseria

Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands

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